Inflammatory Activity on Natalizumab Predicts Short-term but not Long-term Disability in Multiple Sclerosis

BACKGROUND: In people with multiple sclerosis treated with interferon-beta or glatiramer acetate, new MRI lesions and relapses during the first year of treatment predict a poor prognosis. OBJECTIVE: To study this association in those receiving natalizumab. METHODS: Data were collected on relapses, new MRI activity, and Modified Rio Score after initiation of natalizumab in an observational cohort of 161 patients with high baseline disability. These were correlated with Expanded Disability Status Scale (EDSS) progression at years 1, 2, 3, and 3-7 after treatment initiation, versus pre-treatment baseline. RESULTS: 46/161 patients had a relapse in the first year and 44/161 had EDSS progression by year 2. Relapses and Modified Rio Score in the first year of treatment predicted EDSS progression at year 1 and 2 after treatment initiation. However, this effect disappeared with longer follow-up. Paradoxically, there was a trend towards inflammatory activity on treatment (first year Modified Rio Score, relapses, and MRI activity) predicting a lower risk of EDSS progression by years 3-7, although this did not reach statistical significance. Those with and without EDSS progression did not differ in baseline age, EDSS, or pre-treatment relapse rate. Relapses in year 0-1 predicted further relapses in years 1-3. CONCLUSIONS: Breakthrough inflammatory activity after natalizumab treatment is predictive of short-term outcome measures of relapses or EDSS progression, but does not predict longer term EDSS progression, in this cohort with high baseline disability

Tangling clustering of inertial particles in stably stratified turbulence

We have predicted theoretically and detected in laboratory experiments a new type of particle clustering (tangling clustering of inertial particles) in a stably stratified turbulence with imposed mean vertical temperature gradient. In this stratified turbulence a spatial distribution of the mean particle number density is nonuniform due to the phenomenon of turbulent thermal diffusion, that results in formation of a gradient of the mean particle number density, \nabla N, and generation of fluctuations of the particle number density by tangling of the gradient, \nabla N, by velocity fluctuations. The mean temperature gradient, \nabla T, produces the temperature fluctuations by tangling of the gradient, \nabla T, by velocity fluctuations. These fluctuations increase the rate of formation of the particle clusters in small scales. In the laboratory stratified turbulence this tangling clustering is much more effective than a pure inertial clustering that has been observed in isothermal turbulence. In particular, in our experiments in oscillating grid isothermal turbulence in air without imposed mean temperature gradient, the inertial clustering is very weak for solid particles with the diameter 10 microns and Reynolds numbers Re =250. Our theoretical predictions are in a good agreement with the obtained experimental results.Comment: 16 pages, 4 figures, REVTEX4, revised versio

A pattern matching technique for measuring sediment displacement levels

This paper describes a novel technique for obtaining accurate, high (spatial) resolution measurements of sediment redeposition levels. A sequence of different random patterns are projected onto a sediment layer and captured using a high-resolution camera, producing a set of reference images. The same patterns are used to obtain a corresponding sequence of deformed images after a region of the sediment layer has been displaced and redeposited, allowing the use of a high-accuracy pattern matching algorithm to quantify the distribution of the redeposited sediment. A set of experiments using the impact of a vortex ring with a glass ballotini particle layer as the resuspension mechanism are described to test and illustrate the technique. The accuracy of the procedure is assessed using a known crater profile, manufactured to simulate the features of the craters observed in the experiments

Mixing at the external boundary of a submerged turbulent jet

We study experimentally and theoretically mixing at the external boundary of a submerged turbulent jet. In the experimental study we use Particle Image Velocimetry and an Image Processing Technique based on the analysis of the intensity of the Mie scattering to determine the spatial distribution of tracer particles. An air jet is seeded with the incense smoke particles which are characterized by large Schmidt number and small Stokes number. We determine the spatial distributions of the jet fluid characterized by a high concentration of the particles and of the ambient fluid characterized by a low concentration of the tracer particles. In the data analysis we use two approaches, whereby one approach is based on the measured phase function for the study of the mixed state of two fluids. The other approach is based on the analysis of the two-point second-order correlation function of the particle number density fluctuations generated by tangling of the gradient of the mean particle number density by the turbulent velocity field. This gradient is formed at the external boundary of a submerged turbulent jet. We demonstrate that PDF of the phase function of a jet fluid penetrating into an external flow and the two-point second-order correlation function of the particle number density do not have universal scaling and cannot be described by a power-law function. The theoretical predictions made in this study are in a qualitative agreement with the obtained experimental results.Comment: 13 pages, 13 figures, REVTEX

Hysteresis phenomenon in turbulent convection

Coherent large-scale circulations of turbulent thermal convection in air have been studied experimentally in a rectangular box heated from below and cooled from above using Particle Image Velocimetry. The hysteresis phenomenon in turbulent convection was found by varying the temperature difference between the bottom and the top walls of the chamber (the Rayleigh number was changed within the range of $10^7 - 10^8$). The hysteresis loop comprises the one-cell and two-cells flow patterns while the aspect ratio is kept constant ($A=2 - 2.23$). We found that the change of the sign of the degree of the anisotropy of turbulence was accompanied by the change of the flow pattern. The developed theory of coherent structures in turbulent convection (Elperin et al. 2002; 2005) is in agreement with the experimental observations. The observed coherent structures are superimposed on a small-scale turbulent convection. The redistribution of the turbulent heat flux plays a crucial role in the formation of coherent large-scale circulations in turbulent convection.Comment: 10 pages, 9 figures, REVTEX4, Experiments in Fluids, 2006, in pres

The Fungicide Chlorothalonil Is Nonlinearly Associated with Corticosterone Levels, Immunity, and Mortality in Amphibians

Background: Contaminants have been implicated in declines of amphibians, a taxon with vital systems similar to those of humans. However, many chemicals have not been thoroughly tested on amphibians or do not directly kill them

Longitudinal assessment of multiple sclerosis with the brain-age paradigm

OBJECTIVE: During the natural course of MS, the brain is exposed to ageing as well as disease effects. Brain ageing can be modelled statistically; the so-called 'brain-age' paradigm. Here, we evaluated whether brain-predicted age difference (brain-PAD) was sensitive to the presence of MS, clinical progression and future outcomes. METHODS: In a longitudinal, multi-centre sample of 3,565 MRI scans, in 1,204 MS and clinically-isolated syndrome (CIS) patients and 150 healthy controls (mean follow-up time: patients 3.41 years, healthy controls 1.97 years), we measured 'brain-predicted age' using T1-weighted MRI. We compared brain-PAD between MS and CIS patients and healthy controls, and between disease subtypes. Relationships between brain-PAD and Expanded Disability Status Scale (EDSS) were explored. RESULTS: MS patients had markedly higher brain-PAD than healthy controls (mean brain-PAD +10.3 years [95% CI 8.5, 12.1] versus 4.3 years [-2.1, 6.4], p < 0.001). The highest brain-PADs were in secondary-progressive MS (+19.4 years [17.1, 21.9]). Brain-PAD at study entry predicted time-to-disability progression (hazard ratio 1.02 [1.01, 1.03], p < 0.001); though normalised brain volume was a stronger predictor. Greater annualised brain-PAD increases were associated with greater annualised EDSS score (r = 0.26, p < 0.001). INTERPRETATION: The brain-age paradigm is sensitive to MS-related atrophy and clinical progression. A higher brain-PAD at baseline was associated with more rapid disability progression and the rate of change in brain-PAD related to worsening disability. Potentially, 'brain-age' could be used as a prognostic biomarker in early-stage MS, to track disease progression or stratify patients for clinical trial enrolment. This article is protected by copyright. All rights reserved

Quantitative imaging of concentrated suspensions under flow

We review recent advances in imaging the flow of concentrated suspensions, focussing on the use of confocal microscopy to obtain time-resolved information on the single-particle level in these systems. After motivating the need for quantitative (confocal) imaging in suspension rheology, we briefly describe the particles, sample environments, microscopy tools and analysis algorithms needed to perform this kind of experiments. The second part of the review focusses on microscopic aspects of the flow of concentrated model hard-sphere-like suspensions, and the relation to non-linear rheological phenomena such as yielding, shear localization, wall slip and shear-induced ordering. Both Brownian and non-Brownian systems will be described. We show how quantitative imaging can improve our understanding of the connection between microscopic dynamics and bulk flow.Comment: Review on imaging hard-sphere suspensions, incl summary of methodology. Submitted for special volume 'High Solid Dispersions' ed. M. Cloitre, Vol. xx of 'Advances and Polymer Science' (Springer, Berlin, 2009); 22 pages, 16 fig